The overall objective of our proposed research is the development of a safe, efficient and economical method for the treatment of various types of cancers and other disorders. Specifically, we wish to demonstrate the efficacy of therapeutic enzymes chemically linked to collagen materials. Towards this end, we have bound the candidate enzyme L-asparaginase to reconstituted collagen membranes for inclusion in an extracorporeal device and to bovine collagen arterial heterografts for implantation as enzymatically active vascular prostheses. Previous work has demonstrated the effectiveness of extracorporeal perfusion with collagen-bound asparaginase in reducing serum asparaginase levels with minimal damage to blood components. Preliminary studies with collagen-asparaginase vascular prostheses show reductions of serum asparagine in healthy dogs of more tha 80% for periods of 4 to 6.5 days. In all cases, grafts lost patency in 5 to 13 days. Basic studies have enabled us to increase the activity and mechanical strength of the grafts. Our goals for the coming year include: (a) preparation and implantation of improved collagen-asparaginase grafts; (b) preparation and implantation of urokinase-asparaginase collagen grafts to test the effect of a bound fibrinolytic agent on extending the active period of bound asparaginase after implantation; and (c) preparation and evaluation of collagen complexes with phenylalanine ammonia lyase.